Ocuphire Announces Publication of MIRA-1 Phase 2b Results Demonstrating Reduction of Pharmacologically Induced Mydriasis by Nyxol

Ocuphire Pharma announced that the results from the MIRA-1 (NCT04024891) phase 2b clinical trial evaluating the safety and efficacy of Nyxol in the reversal of mydriasis have been published in Optometry and Visual Science. The article will appear in the print edition and is available on-line atwww.optvissci.com.

“The continued peer-reviewed publications of our Nyxol clinical trial results allow us to highlight the iris dilator mechanism and emerging product profile of Nyxol,” Mina Sooch, MBA, President and CEO of Ocuphire Pharma, said in a company news release. “The findings of the MIRA-1 trial specifically demonstrate the potential of Nyxol to offer a safe and effective option for the reversal of mydriasis indication, for which there are presently no FDA approved therapies. The recently enrolled MIRA-2 Phase 3 pivotal trial leveraged the design and findings of the MIRA-1 Phase 2b trial.”

The paper, titled “Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial,” reported the following key findings:

• In the Nyxol treatment group, 29% of subjects met with statistical significance return to within 0.2 mm of their baseline pupil diameter (PD) at 2 hours, compared with 13% in the placebo group. A significant difference was also seen at 4 hours and was independent of mydriatic agent.
• Nyxol eye drops demonstrated a significant improvement over placebo in reducing pupil diameter at 2 hours from the time of maximum pupil diameter, regardless of mydriatic agent. A significant improvement was also seen at 1, 4, and 6 hours.
• Treatment with Nyxol eye drops led to a reduction in time to return to baseline pupil diameter of nearly 2 hours when compared to placebo.
• When treated with Nyxol eye drops, 63% of subjects returned to their accommodative baseline 2 hours after tropicamide-induced mydriasis, a statistically significant increase relative to 38% of subjects treated with placebo.
• Nyxol eye drops demonstrated a favorable safety profile, with roughly one third of subjects experiencing mild conjunctival redness, but no other systemic or ocular adverse effects. Moreover, whether given Nyxol or placebo, any discomfort occurring after treatment was mild in intensity.

“Many of my patients explain how frustrated they are by the lasting and disruptive effects of pupil dilation,” Paul Karpecki OD, Director of Cornea Services for the Kentucky Eye Institute, said in the news release. “The results from the MIRA-1 phase 2b trial demonstrate that Nyxol continues to be a promising candidate that might offer a solution that could greatly improve the patient experience after dilated eye exams.”

Highlights of this double-masked, randomized, placebo-controlled, multicenter phase 2b clinical trial were presented at the 2020 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) by Dr. Karpecki via video submission. For more information on the MIRA-1 trial design, refer to Clinicaltrials.gov NCT04024891.

The MIRA-1 results informed the trial design of the phase 3 MIRA-2 registration trial that recently completed recruitment. MIRA-2 is designed as a multicenter, randomized, double-masked, placebo-controlled, parallel, 24-hour phase 3 trial that planned 168 healthy subjects, and ultimately enrolled 185 subjects. The primary efficacy endpoint for MIRA-2 is the percentage of subjects (study eyes) returning to within 0.2 mm of baseline pupil diameter at 90 minutes. Ophthalmic secondary efficacy endpoints include the percentage of subjects returning to baseline PD at other timepoints, mean change in pupil diameter from mydriatic maximum at multiple timepoints, and percent of subjects returning to baseline accommodation (with tropicamide). Efficacy endpoints will be analyzed at all timepoints and stratified by mydriatic agent and iris color. Safety assessments will include heart rate (HR), blood pressure (BP), conjunctival redness, and tolerability. For more information on the MIRA-2 trial design, refer to Clinicaltrials.gov NCT04620213.

There are 3 noteworthy design differences between the MIRA-2 and MIRA-1 trials. First, the MIRA-1 trial was conducted only in dark irides, which are less responsive to both dilating agents and alpha-1 blocking agents (such as Nyxol). MIRA-2 enrolled an equal number of subjects with light and dark irides. Second, in MIRA-2, two drops of Nyxol were administered in the study eye compared to one drop of Nyxol in MIRA-1. Third, MIRA-2 is employing a 3:1:1 phenylephrine:tropicamide:paremyd randomization schema for mydriatic agents rather than 1:1 phenylephrine:tropicamide in MIRA-1. In MIRA-1, it was shown that phenylephrine-induced mydriasis reverses faster upon administration of Nyxol. Topline results for the phase 3 MIRA-2 registration trial are expected in March 2021.